A new platform to study the molecular mechanisms of exocytosis

Aviv Mezer, Esther Nachliel*, Menachem Gutman, Uri Ashery

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

The exocytotic process in neurons and neuroendocrine cells consists of a sequence of reactions between well defined proteins. In the present study, we have created for the first time a comprehensive kinetic model that demonstrates the dynamics of interactions between key synaptic proteins that are associated with exocytosis. The interactions between the synaptic proteins were transformed into differential rate equations that, after their integration over time, reconstructed the experimental signal. The model can perfectly reconstruct the kinetics of exocytosis, the calcium-dependent priming and fusion processes, and the effects of genetic manipulation of synaptic proteins. The model suggests that fusion occurs from two parallel pathways and assigns precise, non-identical synaptic protein complexes to the two pathways. In addition, it provides a unique opportunity to study the dynamics of intermediate protein complexes during the fusion process, a possibility that is hidden in most experimental systems. We thus developed a novel approach that allows detailed characterization of the temporal relationship between synaptic protein complexes. This model provides an excellent platform for prediction and quantification of the effects of protein manipulations on exocytosis and opens new avenues for experimental investigation of exocytosis.

Original languageAmerican English
Pages (from-to)8838-8846
Number of pages9
JournalJournal of Neuroscience
Volume24
Issue number40
DOIs
StatePublished - 6 Oct 2004
Externally publishedYes

Keywords

  • Chemical kinetic
  • Chromaffin cell
  • Exocytosis
  • Modeling
  • Secretion
  • Synaptic proteins

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